Understanding of the behavioral, cognitive, neurological and biological underpinnings of frontotemporal 1obar degeneration (FTLD) remains fragmentary, but a dramatic paradigm shift in basic and clinical research into the etiology and neuropathology of FTLDs occurred in 1998 with the discoveries of tau gene mutations that were shown to be pathogenic for familial frontotemporal dementia linked to chromosome 17 (FTDP-17) in multiple kindreds, including those with diverse syndromes known descriptively as pallido-ponto-nigral degeneration, Pick's disease, and dementia-disinhibition-parkinsonism-amyotrophy complex. While some of these kindreds were previously thought to represent familial Alzheimer's disease (AD), the hallmark neuropathology of these syndromes and several other sporadic FTLDs was demonstrated to be characterized by prominent accumulations of abnormal tau proteins, and these disorders are collectively known as tauopathies. Prompted by these remarkable advances, the goals of this Program Project Grant (PPG) are to determine the genetic, clinical and imaging features of FTLDs, especially those features that distinguish FTLDs from AD, other dementias, and normal aging. Thus, to support accomplishment of these goals, the key functions of the Neuropathology Core in this PPG are to provide diagnostic histopathological and biochemical evaluations of postmortem brains from subjects followed by PPG investigators, enter all information obtained from these analyses in a secure and confidential database, and provide data from the Neuropathology Core to PPG investigators to facilitate elucidation of the defining genotypic and phenotypic features of hereditary and sporadic FTLDs. Thus, the Neuropathology Core performs critical functions in support of the mission of this PPG to increase understanding of FTLD and related tauopathies.